title: Influences of treatment of early pregnant mares with the progestin altrenogest on embryonic development and gene expression in the endometrium and conceptus.
abstract: A positive influence of altrenogest treatment on a retarded development of the conceptus around the beginning of placentation in mares older than 8 years could be recently demonstrated. In the present study, effects of altrenogest treatment in early-pregnant mares on conceptus development and expression of endometrial and embryonic genes were investigated. Genes were chosen according to a possible involvement in embryo-maternal interaction and embryonic development in the equine species. Mares were treated with altrenogest (0.044 mg/kg bodyweight) or sunflower oil (placebo) from day 5 to 11 after ovulation. Embryos (altrenogest n = 13, placebo n = 12) and biopsies were collected on day 11. Pregnancy rate and embryonic size were not influenced by treatment (embryonic diameter: altrenogest 7.0 ± 2.5, placebo 6.5 ± 1.7 mm, n.s.). The percentage of luminal epithelial cells, superficial glandular epithelial cells and interstitial cells with nuclei staining positively for the progesterone receptor was significantly lower (P < 0.05) in samples collected from altrenogest-treated than from placebo-treated mares (e.g., luminal epithelium: altrenogest 1.9 ± 1.7%, placebo 23.0 ± 10.5%, P < 0.05). Staining for COX2 (cyclooxygenase-2) was not affected by treatment. In the endometrium a slight but significant increase in the number of PMN (polymorph nuclear neutrophils) was seen in response to treatment (altrenogest 0.8 ± 0.5 PMN/field, placebo 0.3 ± 0.3 PMN/field; P < 0.05). No differences in the relative gene expression of COX2, the receptors for progesterone, estrogens and growth hormone as well as for IGF (insulin-like growth factor) 1 and 2 were detected. The relative gene expression of aquaporin 3 in relation to β-actin differed significantly (P < 0.05) between embryos from altrenogest (3.2 ± 0.8) and placebo-treated mares (1.3 ± 0.2), but no other genes were affected. The study demonstrates down-regulation of progesterone receptors in the endometrium of early pregnant mares by treatment with the progestin altrenogest. This increased expression of aquaporin 3 in the conceptus was not related to changes in embryonic size or development.
authors.affiliation: Graf Lehndorff Institute for Equine Science, Brandenburg State Stud, Neustadt (Dosse), Germany.
authors.forename: C
authors.initials: C
authors.lastname: Willmann
authors.forename: S
authors.initials: S
authors.lastname: Budik
authors.forename: I
authors.initials: I
authors.lastname: Walter
authors.forename: C
authors.initials: C
authors.lastname: Aurich
mesh_terms: D000818:Animals; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D006736:Horses / Q000196:embryology* / Q000235:genetics; D011247:Pregnancy; D018873:Pregnancy Rate; D045167:Progesterone Congeners / Q000494:pharmacology*; D014204:Trenbolone Acetate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014327:Trophoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D045167:Progesterone Congeners; C023445:altrenogest; D014204:Trenbolone Acetate